1-193142098-TGAGAGAGA-TGAGA

Position:

• chr1-193142098-TGAGAGAGA-TGAGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_024529.5(CDC73):​c.729+48_729+51delAGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,415,542 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: CDC73 NM_024529.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

Genes affected

CDC73 (HGNC:16783): (cell division cycle 73) This gene encodes a tumor suppressor that is involved in transcriptional and post-transcriptional control pathways. The protein is a component of the the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex. This protein appears to facilitate the association of 3' mRNA processing factors with actively-transcribed chromatin. Mutations in this gene have been linked to hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and parathyroid carcinoma. [provided by RefSeq, Jul 2009]

CDC73 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000148 (22/148670) while in subpopulation SAS AF= 0.000212 (1/4708). AF 95% confidence interval is 0.000126. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC73	NM_024529.5	c.729+48_729+51delAGAG		intron_variant		ENST00000367435.5	NP_078805.3
CDC73	XM_006711537.5	c.729+48_729+51delAGAG		intron_variant			XP_006711600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC73	ENST00000367435.5	c.729+48_729+51delAGAG		intron_variant		1	NM_024529.5	ENSP00000356405.4

Frequencies

GnomAD3 genomes AF: 0.000148 AC: 22 AN: 148670 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000209

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00150 AC: 1905 AN: 1266872 Hom.: 0 AF XY: 0.00137 AC XY: 872 AN XY: 636814

Gnomad4 AFR exome AF: 0.00103

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.000868

Gnomad4 EAS exome AF: 0.000898

Gnomad4 SAS exome AF: 0.000773

Gnomad4 FIN exome AF: 0.000574

Gnomad4 NFE exome AF: 0.00170

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.000148 AC: 22 AN: 148670 Hom.: 0 Cov.: 32 AF XY: 0.000152 AC XY: 11 AN XY: 72406

Gnomad4 AFR AF: 0.000123

Gnomad4 AMR AF: 0.000134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000209

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs80356646; hg19: chr1-193111228;